title: Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects.
abstract: Benznidazole (Bz) and Nifurtimox (Nfx) have been used to treat Chagas disease. As recent studies have de-monstrated cardiotoxic effects of Nfx, we attempted to determine whether Bz behaves similarly. Bz reached the heart tissue of male rats after intragastric administration. No cytosolic Bz nitroreductases were detected, although microsomal NADPH-dependent Bz nitroreductase activity was observed, and appeared to be mediated by P450 reductase. No ultrastructurally observable deleterious effects of Bz were detected, in contrast to the overt cardiac effects previously reported for Nfx. In conclusion, when these drugs are used in chagasic patients, Bz may pose a lesser risk to heart function than Nfx when any cardiopathy is present.
authors.affiliation: Centro de Investigaciones Toxicológicas (CEITOX-CITEFA/CONICET), Villa Martelli, Buenos Aires, Argentina.
authors.forename: María Montalto de
authors.initials: MM
authors.lastname: Mecca
authors.forename: Laura C
authors.initials: LC
authors.lastname: Bartel
authors.forename: Carmen Rodríguez de
authors.initials: CR
authors.lastname: Castro
authors.forename: José A
authors.initials: JA
authors.lastname: Castro
mesh_terms: D000818:Animals; D001711:Biotransformation; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000187:drug effects*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism*; D009547:Nifurtimox / Q000009:adverse effects / Q000493:pharmacokinetics*; D009593:Nitroimidazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D009601:Nitroreductases / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014344:Trypanocidal Agents / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D009601:Nitroreductases; D009547:Nifurtimox; C009999:benzonidazole